Multiple genetic factors in the heterogeneity of thyroid hormone resistance

Journal Article · Fri Jan 01 04:00:00 EST 1993 · Journal of Clinical Endocrinology and Metabolism; (United States)

DOI:https://doi.org/10.1210/jc.76.1.257· OSTI ID:6570537

Weiss, R E; Refetoff, S ^[1]; Marcocci, C; Bruno-Bossio, G ^[2]

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1. Univ. of Chicago, IL (United States)
2. Univ. of Pisa (Italy)

Generalized resistance to thyroid hormone (GRTH), a syndrome of inherited tissue hyposensitivity to thyroid hormone, is linked to thyroid hormone receptor (TR) mutations. A typical feature of GRTH is variable severity of organ involvement among families that, surprisingly, does not correlate with the degree of T[sub 3]-binding impairment of the corresponding in vitro synthesized mutant TRs. Furthermore, variations in the clinical severity among family members harboring identical TR[beta] mutations have been reported. The authors compared serum levels of thyroid hormones that maintained a normal TSH in members of a large family with GRTH divided in three groups: Group A, 8 affected subjects with a mutation replacing arginine-320 with a histidine in the T[sub 3]-binding domain of TR[beta]; Group B, 11 first degree relatives (sibs and children of affected subjects) with no TR[beta] mutation; Group C, 16 controls related by marriage. TSH values were not different among the three groups. As expected, total and free T[sub 4] and T[sub 3], and rT[sub 3] levels were significantly higher in Group A vs Groups B and C. However, with the exception of T[sub 3], the same tests were also significantly higher in Group B vs Group C. The latter differences are not due to thyroid hormone transport in serum since TBG concentrations were not different. It is postulated that genetic variability of factors that contribute to the action of thyroid hormone modulate the phenotype of GRTH associated with TR[beta] mutations. 23 refs., 2 figs., 1 tab.

• OSTI ID: 6570537
• Journal Information: Journal of Clinical Endocrinology and Metabolism; (United States), Journal Name: Journal of Clinical Endocrinology and Metabolism; (United States) Vol. 76:1; ISSN JCEMAZ; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
CARBOXYLIC ACIDS
DISEASES
ENDOCRINE DISEASES
GENE MUTATIONS
HORMONES
MEMBRANE PROTEINS
MUTATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
PEPTIDE HORMONES
PROTEINS
RECEPTORS
THYROID HORMONES
THYROXINE
TRIIODOTHYRONINE